Reduction of Late Urinary Toxicity from Prostate Cancer Radiotherapy via Intrafractional MV-kV Image Guidance

Prostate cancer localization during radiotherapy is difficult and introduces positional variability during treatment. Here we evaluate the impact on treatment toxicities of an in-house system that uses MV and kV imaging guidance (MKIG) to track implanted fiducials during stereotactic body radiotherapy (SBRT) for localized prostate cancer.A 3D MKIG platform that tracks prostate implanted fiducials in real-time was built and clinically translated to replace a prior commercial approach called intrafraction motion review (IMR), which tracks thefiducials in 2D kV view only. MKIG has been shown to correct both superior-inferior and anterior-posterior (AP) motions that are harmful to critical organs and is superior to IMR for intrafractional motion management, which is less sensitive to AP motions. From 2017 to 2019, 150 patients with localized prostate cancer were treated with SBRT to 40 Gy in 5 fractions. During the delivery of volumetric modulated arc therapy, orthogonal MV-kV pairs were simultaneously acquired at every 20° gantry rotation and rigidly registered to the reference image templates created from the planning CT. Calculated 3D translations of implanted fiducials were used to localize the prostate and alert the therapist to interrupt and reposition the prostate when exceeding a 1.5-2 mm threshold. A comparison cohort of 121 prostate patients was treated from 2015 to 2016 with the same prescription dose and treatment technique but instead managed by IMR, where the therapist interrupted treatment based on a 2mm expansion of the fiducial contours superimposed on the kV images. Statistics of intrafractional interruptions, patient shifts, and overall delivery time were collected to evaluate the efficacy of the clinical workflow. The incidence of late grade ≥2 toxicities was analyzed to assess clinical complications. The median follow-up time was 5.5 years (range of 3.6 to 8.0 years).The MKIG cohort had more interruptions per fraction (1.09 vs. 0.28) and longer average delivery time per fraction (579±205s vs. 357±117s) than IMR. 75% of shifts resulting from MKIG were less than 3mm, compared to 51% in IMR, indicating that MKIG tended to detect and correct smaller deviations (p<0.001). The baseline International Prostate Symptom Score was 7.9 in the MKIG cohort vs. 8.4 in IMR (p = 0.41). The incidence of late grade ≥2 urinary toxicity was lower in the MKIG than IMR cohort: 10.7% vs. 19.8% (p = 0.05). One grade ≥2 rectal toxicity was observed in the IMR cohort but none in MKIG.Wehave demonstrated that MKIG is a clinically practical and effective method for monitoring and correcting prostate positional deviations during SBRT of prostate cancer. MKIG is better suited than 2D IMR to localize the prostate and trigger patient repositioning during treatment. A statistically and clinically significant reduction in urinary toxicity was observed. The potential expansion of MKIG to other clinical sites and translation to other centers should be considered.